The impact of Lactobacillus acidophilus on hepatic and colonic fibrosis induced by ethephon in a rat model

Document Type: Original Article


1 Biochemistry Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt

2 Pathology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt

3 Clinical Pathology Department, Faculty of Veterinary Medicine, Zagazig University, Egypt


Objective(s): The study is aimed to elucidate the impact of antioxidant, anti-inflammatory and antifibrosis properties of Lactobacillus acidophilus (L. acidophilus) on liver and colon in ethephon treated rats through measuring Pro- inflammatory cytokines, oxidative stress index, lysosomal cathepsin-D enzyme activity and fibrosis markers.
Materials and Methods: Rats divided into three groups; Group 1: distilled water control, Group 2: rats at day 16 from experiment beginning were orally received ethephon 50 mg/ kg BW in distilled water once daily for 60 days.  Group 3: rats were orally received L. acidophilus enriched diet 1% (w/w) for 15 days as prophylactic, then received both L. acidophilus enriched diet 1% (w/w) and ethephon 50 mg/kg BW for 60 days.
Results: Ethephon exerts hepatic and colonic oxidative stress, inflammatory response and fibrosis through NF-κB activation. On contrary, L. acidophilus supplementation evokes hepatoprotective properties as revealed by decreased serum AST, ALT, γ -GT and increased IGF-1. L. acidophilus exerts antioxidant and anti-inflammatory properties as indicated by decreased TOS, OSI, TNF-α, IL-1β, cathepsins D activity, NF-κB expression and increased TAC, lysosomal membrane stability. L. acidophilus shows antifibrotic activity as demonstrated by down-regulation of TGF-β1, α-SMA, collagen expression.
Conclusion: L. acidophilus possess antioxidant, anti -inflammatory and antifibrotic activity through inhibition of NF-kB.


Main Subjects

1. Baiocchini A, Montaldo C, Conigliaro A, Grimaldi A, Correani V, Mura F, et al. Extracellular matrix molecular remodeling in human liver fibrosis evolution. PLoS One 2016; 11:0151736-0151750.
2. Burke JP, Mulsow JJ, O’Keane C, Docherty NG, Watson RW, O’Connell PR. Fibrogenesis in crohn’s disease. Am J Gastroenterol 2007; 102:439–448.
3. Segall Y, Grendell RL, Toia RF, Casida JE. Composition of technical ethephon (2-chloroethylphosphonic acid) and some analogs relative to their reactivity and biological activity. J Agric Food Chem 1991; 39:380-385.
4. Kader AA. Post-harvest technology of horticultural crops. 3rd ed. University of California, Agriculture and Natural Resources Publication; 2002.p. 535.
5. Per S, Kurtoglu F, Yagmur H, Gümüs K S, Poyrazoglu M. Calcium carbide poisoning via food in childhood. J Emerg Med 2007; 32:179–180.
6. Hassan MK, Chowdhury BLD, Akhtar N. Post-harvest loss assessment: a study to formulate policy for loss reduction of fruits and vegetables and socioeconomic uplift of the stakeholders. Final Rep 2010; 16:166-167.
7. Hakim MDA, Obidul HAK, Alam M, Khatib A, Saha BK, Formuzul HKM, et al. Role of health hazardous ethephone in nutritive values of selected pineapple, banana and tomato. J Food Agric Environ 2012; 10:247-251.
8. Dutta U. Evaluation of ethephon induced oxidative stress to gonadal disorder and its amelioration by ethanolic extract of shoot of Bambusa balcooa Roxb. in Albino rat. Toxicol Lett 2015; 238:269-270.
9. Nada HAA. Mutagenic effects of ethephon on albino mice. J Biol Sci 2006; 6:1041-1046.
10. Tudor M, Cuciureanu M, Cuciureanu R, Slencu BG. Experimental evaluation of the action of ethephon and sodium selenite on some hematological parameters in rats. Med Surg J 2017; 121:806-814.
11. De Jong WH, Van Loveren H. Screening of xenobiotics for direct immunotoxicity in an animal study. Method 2007; 41:3–8.
12. Fuller R. Probiotics in man and animal. J Appl Bacteriol 1989; 66:365–378.
13. Yadav H, Jain S, Sinha PR. Antidiabetic effect of probiotic dahi containing Lactobacillus acidophilus and Lactobacillus casei in high fructose fed rats. Nutrition 2007; 23:62-68.
14. Foye TO, Huang IF, Chiou CC, Walker AW, Shi NH. Early administration of probiotic Lactobacillus acidophilus and/or prebiotic inulin attenuates pathogen-mediated intestinal inflammation and Smad 7 cell signaling. FEMS Immunol Med Microbiol 2012; 65:467–480.
15. Hong M, Kim SW, Han SH, Kim DJ, Suk KT, Kim YS, et al. Probiotics (Lactobacillus rhamnosus R0011 and acidophilus R0052) reduce the expression of toll-like receptor 4 in mice with alcoholic liver disease. PLoS One 2015; 10:0117451-0117468.
16. Yazar S, Baydan E. The subchronic toxic effects of plant growth promoters in mice. Ankara Üniv Vet Fak Derg 2008; 55:17-21.
17. Le Leu RK, Brown IL, Hu Y, Bird AR, Jackson M, Esterman A, et al. A synbiotic combination of resistant starch and Bifidobacterium lactis facilitates apoptotic deletion of carcinogen-damaged cells in rat colon. J Nutr Cancer 2005; 135:996-1001.
18. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005; 38:1103-1111.
19. Barret AJ, Heath MF. Lysosomal enzymes, in Lysosome: Laboratory Handbook, J. T. Dingle, Ed., 1977; pp. 124–126.
20. Acharya MM, Khamesra SH, Katyare, SS. Effect of repeated intraperitoneal exposure to picrotoxin on rat liver lysosomal function. Indian J Exp Biol 2004; 42:808–811.
21. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951; 193:265–275.
22. Bancroft JD, Stevens A. Theory and practice of histological techniques1990.
23. .Jones ML, Bancroft JD, Gamble M. Connective tissues and stains. In: Theory and Practice of Histological Techniques 2008.pp. 135-160.
24. Eissa S, Shoman S. Markers of invasion and metastasis and markers of tumor proliferation and apoptosis. In: Tumors Markers. Chapman and Hall, LippincottRaven Publisher Inc, London, UK, 1998.pp. 131-153.
25. Hsu SM, Raine L, Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 1980; 29:577-580.
26. Conchillo M, De Knegt RJ, Payeras M, Quiroga J, Sangro B, Herrero JI, et al. Insulin-like growth factor I (IGF-I) replacement therapy increases albumin concentration in liver cirrhosis: results of a pilot randomized controlled clinical trial. J Hepatol 2005; 43:630-636.
27. Chen HJ, Wu SD, Huang GJ, Shen CY, Afiyanti M, Li WJ, et al. Expression of a cloned sweet potato catalase SPCAT1 alleviates ethephon-mediated leaf senescence and H2O2 elevation. J Plant Pysiol 2012; 169:86–97.
28. Csordas A. Toxicology of butyrate and short-chain fatty acids. In: Hill MJ, ed. Role of Gut Bacteria in Human Toxicology and Pharmacology. London: Taylor and Francis 1995.pp. 105–127.
29. Sario AD, Candelaresi C, Omenetti A, Benedetti A. Vitamin E in chronic liver diseases and liver fibrosis. Vitam Horm 2007; 76:551–573.
30. Chen X, Ying X, Chen L, Zhang W, Zhang Y. Protective effects of sesamin on liver fibrosis through antioxidative and anti-inflammatory activities in rats. Immunopharmacol Immunotoxicol 2015; 37:465–472.
31. Moles A, Tarrats N, Fernandez-Checa JC, Mari M. Cathepsins B and D drive hepatic stellate cell proliferation and promote their fibrogenic potential. Hepatol 2009; 49:1297–1307.
32. EL-Swefy S, Hassanen SI. Improvement of hepatic fibrosis by leukotriene inhibition in cholestatic rats. Ann Hepatol 2009; 8:41–49.
33. Gasull X, Bataller R, Ginès P, Sancho-Bru P, Nicolás JM, Görbig MN, et al. Human myofibroblastic hepatic stellate cells express Ca2+-activated K+ channels that modulate the effects of endothelin-1 and nitric oxide. J Hepatol 2001; 35:739–748.
34. Liu T, Zhang L, Joo D, Sun S. NF-κB signaling in inflammation. Signal Transduct Target Ther 2017; 2:17023.
35. Peran L, Camuesco D, Comalada M, Bailon E, Henriksson A, Xaus J, et al. A comparative study of the preventative effects exerted by three probiotics, Bifidobacterium lactis, Lactobacillus casei and Lactobacillus acidophilus, in the TNBS model of rat colitis. J Appl Microbiol 2007; 103:836–844.
36. Patel B, Kumar P, Banerjee R, Basu M, Pal A, Samanta M, et al. Lactobacillus acidophilus attenuates Aeromonas hydrophila induced cytotoxicity in catla thymus macrophages by modulating oxidative stress and inflammation. Mol Immunol 2016; 75:69–83.
37. Ejtahed HS, Mohtadi-Nia J, Homayouni-Rad A, Niafar M, Asghari-Jafarabadi M, Mofid, V. Probiotic yogurt improves antioxidant status in type 2 diabetic patients. Nutr 2012; 28:539–543.
38. Qiao J, Li H, Wang Z, Wang W. Effects of Lactobacillus acidophilus dietary supplementation on the performance, intestinal barrier function, rectal microflora and serum immune function in weaned piglets challenged with Escherichia coli lipopolysaccharide. Antonie van Leeuwenhoek 2015; 107:883–891.
39. Velayudham A, Dolganiuc A, Ellis M, Petrasek J, Kodys K, Mandrekar P, et al. VSL#3 probiotic treatment attenuates fibrosis without changes in steatohepatitis in a diet-induced nonalcoholic steatohepatitis model in mice. Hepatol 2009; 49:989-997.
40. Lee SI, Kim HS, Koo JM, Kim IH. Lactobacillus acidophilus modulates inflammatory activity by regulating the TLR4 and NF-κB expression in porcine peripheral blood mononuclear cells after lipopolysaccharide challenge. Br J Nutr 2016; 115:567–575.
41. Choi SS, Kim Y, Han KS, You S, Oh S, Kim SH. Effects of Lactobacillus strains on cancer cell proliferation and oxidative stress in vitro. Lett Appl Microbiol 2006; 42:452-458.
42. Karamali M, Dadkhah F, Sadrkhanlou M, Jamilian M, Ahmadi S, Tajabadi-Ebrahimi M, et al. Effects of probiotic supplementation on glycaemia control and lipid profiles in gestational diabetes: a randomized, double-blind, placebo-controlled trial. Diabetes Metab 2016; 42:234-241.
43. Rishi P, Mavi SK, Bharrhan S, Shukla G, Tewari R. Protective efficacy of probiotic alone or in conjunction with a prebiotic in Salmonella-induced liver damage. FEMS Microbiol Ecol 2009; 69:222–230.
44. Amdekar S, Singh V. Lactobacillus acidophilus maintained oxidative stress from reproductive organs in collagen-induced arthritic rats. J Hum Reprod Sci 2016; 9:41–46.
45. Shimizu M, Hashiguchi M, Shiga T, Tamura H, Mochizukim M. Meta-analysis: effects of probiotic supplementation on lipid profiles in normal to mildly hypercholesterolemic individuals. PLoS ONE 2015; 10:0139795-0139811.
46. Fardet A, Rock E. In vitro and In vivo antioxidant potential of milks, yoghurts, fermented milks and cheeses: a narrative review of evidence. Nutr Res Rev J 2018; 31:52-70.